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Physiopathology, Diagnosis, and Treatment of Nonfunctioning Pituitary Adenomas

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Hypothalamic-Pituitary Diseases

Part of the book series: Endocrinology ((ENDOCR))

Abstract

Clinically nonfunctioning pituitary adenomas (NFPAs) include all pituitary adenomas that are not hormonally active and are therefore not associated with clinical syndromes such as amenorrhea-galactorrhea (prolactinomas), acromegaly, Cushing’s disease, or hyperthyroidism (TSH-secreting adenomas). However, most such NFPAs in fact secrete gonadotropins or are actually gonadotroph pituitary adenomas. No univocal pathophysiological mechanism has been demonstrated. NFPA is usually diagnosed in a patient with signs and symptoms related to a mass effect (headache, visual impairment, sometimes pituitary apoplexy). More and more NFPAs are discovered incidentally. Biochemical workup often documents several pituitary insufficiencies. Unless contraindicated or in particular situations (e.g., incidentalomas at distance from optic pathways), surgery is the mainstay of treatment. Resection, generally via a transsphenoidal approach (with the help of an endoscope), should be performed by a neurosurgeon with extensive experience in pituitary surgery, in order to maximize the chances of complete resection and to minimize complications. If a tumor remnant persists (a frequent situation in patients with large and often invasive adenomas), watchful waiting is preferred to routine radiotherapy, as long as the tumor residue does not grow. NFPA can sometimes recur even after complete resection. Postoperative irradiation is only considered in case of residual tumor growth or relapse.

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References

  • Abouaf L, Vighetto A, Lebas M. Neuro-ophthalmologic exploration in non-functioning pituitary adenoma. Ann Endocrinol (Paris). 2015;76(3):210–9. https://doi.org/10.1016/j.ando.2015.04.006.

    Article  Google Scholar 

  • Ammirati M, Wei L, Ciric I. Short-term outcome of endoscopic versus microscopic pituitary adenoma surgery: a systematic review and meta-analysis. J Neurol Neurosurg Psychiatry. 2013;84(8):843–9. https://doi.org/10.1136/jnnp-2012-303194.

    Article  PubMed  Google Scholar 

  • Arafah BM, Kailani SH, Nekl KE, Gold RS, Selman WR. Immediate recovery of pituitary function after transsphenoidal resection of pituitary macroadenomas. J Clin Endocrinol Metab. 1994;79(2):348–54. https://doi.org/10.1210/jcem.79.2.8045946.

    CAS  PubMed  Google Scholar 

  • Arafah BM, Prunty D, Ybarra J, Hlavin ML, Selman WR. The dominant role of increased intrasellar pressure in the pathogenesis of hypopituitarism, hyperprolactinemia, and headaches in patients with pituitary adenomas. J Clin Endocrinol Metab. 2000;85(5):1789–93.

    CAS  PubMed  Google Scholar 

  • Asa SL. Pituitary adenomas. In Asa SL, editors. Tumors of the pituitary gland. Vol. Fourth series fascicle 15. Washington, DC: Armed Forces Institute of Pathology; 2011. p. 55–172.

    Google Scholar 

  • Asa SL, Cheng Z, Ramyar L, Singer W, Kovacs K, Smyth HS, Muller P. Human pituitary null cell adenomas and oncocytomas in vitro: effects of adenohypophysiotropic hormones and gonadal steroids on hormone secretion and tumor cell morphology. J Clin Endocrinol Metab. 1992;74(5):1128–34.

    CAS  PubMed  Google Scholar 

  • Asa SL, Bamberger AM, Cao B, Wong M, Parker KL, Ezzat S. The transcription activator steroidogenic factor-1 is preferentially expressed in the human pituitary gonadotroph. J Clin Endocrinol Metab. 1996;81(6):2165–70.

    CAS  PubMed  Google Scholar 

  • Astradsson A, Wiencke AK, Munck af Rosenschold P, Engelholm SA, Ohlhues L, Roed H, Juhler M. Visual outcome after fractionated stereotactic radiation therapy of benign anterior skull base tumors. J Neuro-Oncol. 2014;118(1):101–8. https://doi.org/10.1007/s11060-014-1399-0.

    Article  Google Scholar 

  • Bahar A, Bicknell JE, Simpson DJ, Clayton RN, Farrell WE. Loss of expression of the growth inhibitory gene GADD45gamma, in human pituitary adenomas, is associated with CpG island methylation. Oncogene. 2004;23(4):936–44.

    Article  CAS  PubMed  Google Scholar 

  • Barkan AL, Chandler WF. Giant pituitary prolactinoma with falsely low serum prolactin: the pitfall of the “high-dose hook effect”: case report. Neurosurgery. 1998;42(4):913–5; discussion 915-916.

    Article  CAS  PubMed  Google Scholar 

  • Bastos RV, Silva CM, Tagliarini JV, Zanini MA, Romero FR, Boguszewski CL, Nunes VD. Endoscopic versus microscopic transsphenoidal surgery in the treatment of pituitary tumors: systematic review and meta-analysis of randomized and non-randomized controlled trials. Arch Endocrinol Metab. 2016;60(5):411–9. https://doi.org/10.1590/2359-3997000000204.

    Article  PubMed  Google Scholar 

  • Beckers A, Stevenaert A, Mashiter K, Hennen G. Follicle-stimulating hormone-secreting pituitary adenomas. J Clin Endocrinol Metab. 1985;61:525–8.

    Article  CAS  PubMed  Google Scholar 

  • Beckers A, Aaltonen LA, Daly AF, Karhu A. Familial isolated pituitary adenomas (FIPA) and the pituitary adenoma predisposition due to mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene. Endocr Rev. 2013;34(2):239–77. https://doi.org/10.1210/er.2012-1013.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bengtsson D, Schroder HD, Andersen M, Maiter D, Berinder K, Feldt Rasmussen U, … Burman P. Long-term outcome and MGMT as a predictive marker in 24 patients with atypical pituitary adenomas and pituitary carcinomas given treatment with temozolomide. J Clin Endocrinol Metab. 2015;100(4):1689–98. https://doi.org/10.1210/jc.2014-4350.

  • Bir SC, Murray RD, Ambekar S, Bollam P, Nanda A. Clinical and radiologic outcome of gamma knife radiosurgery on nonfunctioning pituitary adenomas. J Neurol Surg B Skull Base. 2015;76(5):351–7. https://doi.org/10.1055/s-0035-1549309.

    Article  PubMed  PubMed Central  Google Scholar 

  • Black PM, Jameson JL, Hsu DN, Klibanski A, Hedley-Whyte ET, Ridgway EC, … Zervas NT. Hormone products of apparently non functioning pituitary adenomas. In Landolt AM, Heitz PU, Zapf J, Girard J, Del Pozo E, editors. Advances in pituitary adenoma research, vol 69. Oxford: Pergamon Press; 1988. p. 413.

    Google Scholar 

  • Borgato S, Romoli R, Cortelazzi D, Asteria C, Persani L, Beck-Peccoz P. FSH bioactivity and serum inhibin a-a and a-ßa levels in patients with gonadotropinoma and non functioning pituitary adenomas. J Endocrinol Investig. 1996;19(Suppl to 5):34. (Abstract).

    Google Scholar 

  • Bostrom JP, Meyer A, Pintea B, Gerlach R, Surber G, Lammering G, Hamm K. Risk-adapted single or fractionated stereotactic high-precision radiotherapy in a pooled series of nonfunctioning pituitary adenomas: high local control and low toxicity. Strahlenther Onkol. 2014;190(12): 1095–103. https://doi.org/10.1007/s00066-014-0715-0.

    Article  PubMed  PubMed Central  Google Scholar 

  • Brada M, Rajan B, Traish D, Ashley S, Holmes-Sellors PJ, Nussey S, Uttley D. The long-term efficacy of conservative surgery and radiotherapy in the control of pituitary adenomas. Clin Endocrinol. 1993;38(6):571–8.

    Article  CAS  Google Scholar 

  • Brada M, Burchell L, Ashley S, Traish D. The incidence of cerebrovascular accidents in patients with pituitary adenoma. Int J Radiat Oncol Biol Phys. 1999;45(3):693–8.

    Article  CAS  PubMed  Google Scholar 

  • Brada M, Ashley S, Ford D, Traish D, Burchell L, Rajan B. Cerebrovascular mortality in patients with pituitary adenoma. Clin Endocrinol (Oxf). 2002;57(6):713–7.

    Article  CAS  Google Scholar 

  • Briet C, Salenave S, Bonneville JF, Laws ER, Chanson P. Pituitary apoplexy. Endocr Rev. 2015;36(6):622–45. https://doi.org/10.1210/er.2015-1042.

    Article  PubMed  Google Scholar 

  • Brochier S, Galland F, Kujas M, Parker F, Gaillard S, Raftopoulos C, … Chanson P. Factors predicting relapse of nonfunctioning pituitary macroadenomas after neurosurgery: a study of 142 patients. Eur J Endocrinol. 2010;163(2):193–200. https://doi.org/10.1530/EJE-10-0255.

  • Bruno OD, Juarez-Allen L, Christiansen SB, Manavela M, Danilowicz K, Vigovich C, Gomez RM. Temozolomide therapy for aggressive pituitary tumors: results in a small series of patients from Argentina. Int J Endocrinol. 2015;2015:587893. https://doi.org/10.1155/2015/587893.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bush ZM, Longtine JA, Cunningham T, Schiff D, Jane JA Jr, Vance ML, … Lopes MB. Temozolomide treatment for aggressive pituitary tumors: correlation of clinical outcome with O(6)-methylguanine methyltransferase (MGMT) promoter methylation and expression. J Clin Endocrinol Metab. 2010;95(11):E280–90. https://doi.org/10.1210/jc.2010-0441.

  • Castinetti F, Dufour H, Gaillard S, Jouanneau E, Vasiljevic A, Villa C, Trouillas J. Non-functioning pituitary adenoma: when and how to operate? What pathologic criteria for typing? Ann Endocrinol (Paris). 2015;76(3):220–7. https://doi.org/10.1016/j.ando.2015.04.007.

    Article  Google Scholar 

  • Chanson P, Brochier S. Non-functioning pituitary adenomas. J Endocrinol Investig. 2005;28(Suppl 11):93–9.

    CAS  Google Scholar 

  • Chanson P, Maiter D. Prolactinoma. In: Melmed S, editor. The pituitary. 4th ed. San Diego: Elsevier; 2017. p. 467–514.

    Chapter  Google Scholar 

  • Chanson P, Young J. Pituitary incidentalomas. Endocrinologist. 2003;13(2):124–35.

    Article  Google Scholar 

  • Chanson P, Pantel J, Young J, Couzinet B, Bidart JM, Schaison G. Free luteinizing-hormone beta-subunit in normal subjects and patients with pituitary adenomas. J Clin Endocrinol Metab. 1997;82(5):1397–402.

    Article  CAS  PubMed  Google Scholar 

  • Chanson P, De Roux N, Young J, Bidart JM, Jaquet P, Misrahi M, … Schaison G. Absence of activating mutations in the GnRH receptor gene in human pituitary gonadotroph adenomas. Eur J Med. 1998;139:157–60.

    Google Scholar 

  • Chanson P, Raverot G, Castinetti F, Cortet-Rudelli C, Galland F, Salenave S, French Endocrinology Society non-functioning pituitary adenoma work group. Management of clinically non-functioning pituitary adenoma. Ann Endocrinol (Paris). 2015;76(3):239–47. https://doi.org/10.1016/j.ando.2015.04.002.

    Article  Google Scholar 

  • Chen Y, Wang CD, Su ZP, Chen YX, Cai L, Zhuge QC, Wu ZB. Natural history of postoperative nonfunctioning pituitary adenomas: a systematic review and meta-analysis. Neuroendocrinology. 2012;96(4):333–42. https://doi.org/10.1159/000339823.

    Article  CAS  PubMed  Google Scholar 

  • Chen Y, Li ZF, Zhang FX, Li JX, Cai L, Zhuge QC, Wu ZB. Gamma knife surgery for patients with volumetric classification of nonfunctioning pituitary adenomas: a systematic review and meta-analysis. Eur J Endocrinol. 2013;169(4):487–95. https://doi.org/10.1530/EJE-13-0400.

    Article  CAS  PubMed  Google Scholar 

  • Chesnokova V, Zonis S, Rubinek T, Yu R, Ben-Shlomo A, Kovacs K, … Melmed S. Senescence mediates pituitary hypoplasia and restrains pituitary tumor growth. Cancer Res. 2007;67(21): 10564–72.

    Google Scholar 

  • Chesnokova V, Zonis S, Zhou C, Ben-Shlomo A, Wawrowsky K, Toledano Y, … Melmed S. Lineage-specific restraint of pituitary gonadotroph cell adenoma growth. PLoS One. 2011;6(3):e17924. https://doi.org/10.1371/journal.pone.0017924.

  • Chesnokova V, Zonis S, Wawrowsky K, Tani Y, Ben-Shlomo A, Ljubimov V, … Melmed S. Clusterin and FOXL2 act concordantly to regulate pituitary gonadotroph adenoma growth. Mol Endocrinol. 2012;26(12):2092–103. https://doi.org/10.1210/me.2012-1158.

  • Cheunsuchon P, Zhou Y, Zhang X, Lee H, Chen W, Nakayama Y, … Klibanski A. Silencing of the imprinted DLK1-MEG3 locus in human clinically nonfunctioning pituitary adenomas. Am J Pathol. 2011;179(4):2120–30. https://doi.org/10.1016/j.ajpath.2011.07.002.

  • Chiloiro S, Doglietto F, Trapasso B, Iacovazzo D, Giampietro A, Di Nardo F, … Bianchi A. Typical and atypical pituitary adenomas: a single-center analysis of outcome and prognosis. Neuroendocrinology. 2015;101(2):143–50. https://doi.org/10.1159/000375448.

  • Chinezu L, Vasiljevic A, Trouillas J, Lapoirie M, Jouanneau E, Raverot G. Silent somatotroph tumour revisited from a study of 80 patients with and without acromegaly and a review of the literature. Eur J Endocrinol. 2017;176(2):195–201. https://doi.org/10.1530/EJE-16-0738.

    Article  CAS  PubMed  Google Scholar 

  • Colao A, Di Somma C, Pivonello R, Faggiano A, Lombardi G, Savastano S. Medical therapy for clinically non-functioning pituitary adenomas. Endocr Relat Cancer. 2008;15(4):905–15.

    Article  CAS  PubMed  Google Scholar 

  • Colin P, Jovenin N, Delemer B, Caron J, Grulet H, Hecart AC, … Rousseaux P. Treatment of pituitary adenomas by fractionated stereotactic radiotherapy: a prospective study of 110 patients. Int J Radiat Oncol Biol Phys. 2005;62(2):333–41. https://doi.org/10.1016/j.ijrobp.2004.09.058.

  • Comtois R, Beauregard H, Somma M, Serri O, Aris-Jilwan N, Hardy J. The clinical and endocrine outcome to trans-sphenoidal microsurgery of non secreting pituitary adenomas. Cancer. 1991;68:860–6.

    Article  CAS  PubMed  Google Scholar 

  • Cooper O, Geller JL, Melmed S. Ovarian hyperstimulation syndrome caused by an FSH-secreting pituitary adenoma. Nat Clin Pract Endocrinol Metab. 2008;4(4):234–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cortet-Rudelli C, Bonneville JF, Borson-Chazot F, Clavier L, Coche Dequeant B, Desailloud R, … Chanson P. Post-surgical management of non-functioning pituitary adenoma. Ann Endocrinol (Paris). 2015;76(3):228–38. https://doi.org/10.1016/j.ando.2015.04.003.

  • D’Angelo D, Palmieri D, Mussnich P, Roche M, Wierinckx A, Raverot G, … Fusco A. Altered microRNA expression profile in human pituitary GH adenomas: down-regulation of miRNA targeting HMGA1, HMGA2, and E2F1. J Clin Endocrinol Metab. 2012;97(7):E1128–38. https://doi.org/10.1210/jc.2011-3482.

  • Daly AF, Rixhon M, Adam C, Dempegioti A, Tichomirowa MA, Beckers A. High prevalence of pituitary adenomas: a cross-sectional study in the province of Liege, Belgium. J Clin Endocrinol Metab. 2006;91(12):4769–75.

    Article  CAS  PubMed  Google Scholar 

  • Daneshdoost L, Gennarelli TA, Bashey HM, Savino PJ, Sergott RC, Bosley TM, Snyder PJ. Recognition of gonadotroph adenomas in women. N Engl J Med. 1991;324:589–94.

    Article  CAS  PubMed  Google Scholar 

  • Daneshdoost L, Gennarelli TA, Bashey HM, Savino PJ, Sergott RC, Bosley TM, Snyder PJ. Identification of gonadotroph adenomas in men with clinically non functioning adenomas by the luteinizing hormone ß subunit response to thyrotropin-releasing hormone. J Clin Endocrinol Metab. 1993;77:1352–5.

    CAS  PubMed  Google Scholar 

  • Davis JR, McNeilly JR, Norris AJ, Pope C, Wilding M, McDowell G, … McNeilly AS. Fetal gonadotrope cell origin of FSH-secreting pituitary adenoma – insight into human pituitary tumour pathogenesis. Clin Endocrinol (Oxf). 2006;65(5):648–54. https://doi.org/10.1111/j.1365-2265.2006.02644.x.

  • de Laat JM, Dekkers OM, Pieterman CR, Kluijfhout WP, Hermus AR, Pereira AM, … Valk GD. Long-term natural course of pituitary tumors in patients with MEN1: results from the DutchMEN1 Study Group (DMSG). J Clin Endocrinol Metab. 2015;100(9):3288–96. https://doi.org/10.1210/JC.2015-2015.

  • Dehdashti AR, Ganna A, Karabatsou K, Gentili F. Pure endoscopic endonasal approach for pituitary adenomas: early surgical results in 200 patients and comparison with previous microsurgical series. Neurosurgery. 2008;62(5):1006–15. https://doi.org/10.1227/01.neu.0000325862.83961.12; discussion 1015-1007.

    Article  PubMed  Google Scholar 

  • Dekkers OM, Pereira AM, Roelfsema F, Voormolen JH, Neelis KJ, Schroijen MA, … Romijn JA. Observation alone after transsphenoidal surgery for nonfunctioning pituitary macroadenoma. J Clin Endocrinol Metab. 2006;91(5):1796–801.

    Google Scholar 

  • Dekkers OM, Pereira AM, Romijn JA. Treatment and follow-up of clinically nonfunctioning pituitary macroadenomas. J Clin Endocrinol Metab. 2008;93(10):3717–26.

    Article  CAS  PubMed  Google Scholar 

  • Del Basso De Caro M, Solari D, Pagliuca F, Villa A, Guadagno E, Cavallo LM, … Cappabianca P. Atypical pituitary adenomas: clinical characteristics and role of ki-67 and p53 in prognostic and therapeutic evaluation. A series of 50 patients. Neurosurg Rev. 2017;40(1):105–14. https://doi.org/10.1007/s10143-016-0740-9.

  • Dudziak K, Honegger J, Bornemann A, Horger M, Mussig K. Pituitary carcinoma with malignant growth from first presentation and fulminant clinical course–case report and review of the literature. J Clin Endocrinol Metab. 2011;96(9):2665–9. https://doi.org/10.1210/jc.2011-1166.

    Article  CAS  PubMed  Google Scholar 

  • Duong CV, Emes RD, Wessely F, Yacqub-Usman K, Clayton RN, Farrell WE. Quantitative, genome-wide analysis of the DNA methylome in sporadic pituitary adenomas. Endocr Relat Cancer. 2012;19(6):805–16. https://doi.org/10.1530/ERC-12-0251.

    Article  CAS  PubMed  Google Scholar 

  • Dworakowska D, Wlodek E, Leontiou CA, Igreja S, Cakir M, Teng M, … Grossman AB. Activation of RAF/MEK/ERK and PI3K/AKT/mTOR pathways in pituitary adenomas and their effects on downstream effectors. Endocr Relat Cancer. 2009;16(4):1329–38. https://doi.org/10.1677/ERC-09-0101.

  • Elston MS, Gill AJ, Conaglen JV, Clarkson A, Shaw JM, Law AJ, … McDonald KL. Wnt pathway inhibitors are strongly down-regulated in pituitary tumors. Endocrinology. 2008;149(3): 1235–42. https://doi.org/10.1210/en.2007-0542.

  • Erickson D, Scheithauer B, Atkinson J, Horvath E, Kovacs K, Lloyd RV, Young WF Jr. Silent subtype 3 pituitary adenoma: a clinicopathologic analysis of the Mayo Clinic experience. Clin Endocrinol (Oxf). 2009;71(1):92–9.

    Article  CAS  Google Scholar 

  • Erridge SC, Conkey DS, Stockton D, Strachan MW, Statham PF, Whittle IR, … Gregor A. Radiotherapy for pituitary adenomas: long-term efficacy and toxicity. Radiother Oncol. 2009;93(3):597–601. https://doi.org/10.1016/j.radonc.2009.09.011.

  • Ezzat S, Asa SL, Couldwell WT, Barr CE, Dodge WE, Vance ML, McCutcheon IE. The prevalence of pituitary adenomas: a systematic review. Cancer. 2004;101(3):613–9.

    Article  PubMed  Google Scholar 

  • Fan X, Gabbi C, Kim HJ, Cheng G, Andersson LC, Warner M, Gustafsson JA. Gonadotropin-positive pituitary tumors accompanied by ovarian tumors in aging female ERbeta−/− mice. Proc Natl Acad Sci USA. 2010;107(14):6453–8. https://doi.org/10.1073/pnas.1002029107.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Feng J, Yu SY, Li CZ, Li ZY, Zhang YZ. Integrative proteomics and transcriptomics revealed that activation of the IL-6R/JAK2/STAT3/MMP9 signaling pathway is correlated with invasion of pituitary null cell adenomas. Mol Cell Endocrinol. 2016;436:195–203. https://doi.org/10.1016/j.mce.2016.07.025.

    Article  CAS  PubMed  Google Scholar 

  • Fernandez A, Karavitaki N, Wass JA. Prevalence of pituitary adenomas: a community-based, cross-sectional study in Banbury (Oxfordshire, UK). Clin Endocrinol (Oxf). 2009;72:377–82.

    Article  Google Scholar 

  • Fernandez-Balsells MM, Murad MH, Barwise A, Gallegos-Orozco JF, Paul A, Lane MA, … Montori VM. Natural history of nonfunctioning pituitary adenomas and incidentalomas: a systematic review and metaanalysis. J Clin Endocrinol Metab. 2011;96(4):905–12. https://doi.org/10.1210/jc.2010-1054.

  • Ferrante E, Ferraroni M, Castrignano T, Menicatti L, Anagni M, Reimondo G, … Lania AG. Non-functioning pituitary adenoma database: a useful resource to improve the clinical management of pituitary tumors. Eur J Endocrinol. 2006;155(6):823–9.

    Google Scholar 

  • Ferrau F, Romeo PD, Puglisi S, Ragonese M, Torre ML, Scaroni C, … Cannavo S. Analysis of GPR101 and AIP genes mutations in acromegaly: a multicentric study. Endocrine. 2016;54(3): 762–7. https://doi.org/10.1007/s12020-016-0862-4.

  • Filippella M, Galland F, Kujas M, Young J, Faggiano A, Lombardi G, … Chanson P. Pituitary tumour transforming gene (PTTG) expression correlates with the proliferative activity and recurrence status of pituitary adenomas: a clinical and immunohistochemical study. Clin Endocrinol (Oxf). 2006;65(4):536–43. https://doi.org/10.1111/j.1365-2265.2006.02630.x.

  • Freda PU, Beckers AM, Katznelson L, Molitch ME, Montori VM, Post KD, … Endocrine Society. Pituitary incidentaloma: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(4):894–904. https://doi.org/10.1210/jc.2010-1048.

  • Frieze TW, Mong DP, Koops MK. “Hook effect” in prolactinomas: case report and review of literature. Endocr Pract. 2002;8(4):296–303. https://doi.org/10.4158/EP.8.4.296.

    Article  PubMed  Google Scholar 

  • Galland F, Vantyghem MC, Cazabat L, Boulin A, Cotton F, Bonneville JF, … Chanson P. Management of nonfunctioning pituitary incidentaloma. Ann Endocrinol (Paris). 2015;76(3): 191–200. https://doi.org/10.1016/j.ando.2015.04.004.

  • Galway AB, Hsue AJW, Daneshdoost L, Zhou MH, Pavlou SN, Snyder PJ. Gonadotroph adenomas in men produce biologically active follicle-stimulating hormone. J Clin Endocrinol Metab. 1990;71:907–12.

    Article  CAS  PubMed  Google Scholar 

  • Gejman R, Batista DL, Zhong Y, Zhou Y, Zhang X, Swearingen B, … Klibanski A. Selective loss of MEG3 expression and intergenic differentially methylated region hypermethylation in the MEG3/DLK1 locus in human clinically nonfunctioning pituitary adenomas. J Clin Endocrinol Metab. 2008;93(10):4119–25.

    Google Scholar 

  • Gittoes NJL, Bates AS, Tse W, Bullivan B, Sheppard MC, Clayton RN, Stewart PM. Radiotherapy for non-functioning pituitary tumours. Clin Endocrinol. 1998;48:331–7.

    Article  CAS  Google Scholar 

  • Gnanalingham KK, Bhattacharjee S, Pennington R, Ng J, Mendoza N. The time course of visual field recovery following trans-sphenoidal surgery for pituitary adenomas: predictive factors for a good outcome. J Neurol Neurosurg Psychiatry. 2005;76(3):415–9. https://doi.org/10.1136/jnnp.2004.035576.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Greenman Y, Stern N. How should a nonfunctioning pituitary macroadenoma be monitored after debulking surgery? Clin Endocrinol (Oxf). 2009a;70(6):829–32. https://doi.org/10.1111/j.1365-2265.2009.03542.x.

    Article  Google Scholar 

  • Greenman Y, Stern N. Non-functioning pituitary adenomas. Best Pract Res Clin Endocrinol Metab. 2009b;23(5):625–38.

    Article  CAS  PubMed  Google Scholar 

  • Greenman Y, Tordjman K, Kisch E, Razon N, Ouaknine G, Stern N. Relative sparing of anterior pituitary function in patients with growth hormone-secreting macroadenomas: comparison with nonfunctioning macroadenomas. J Clin Endocrinol Metab. 1995;80(5):1577–83.

    CAS  PubMed  Google Scholar 

  • Greenman Y, Ouaknine G, Veshchev I, Reider G II, Segev Y, Stern N. Postoperative surveillance of clinically nonfunctioning pituitary macroadenomas: markers of tumour quiescence and regrowth. Clin Endocrinol (Oxf). 2003;58(6):763–9.

    Article  CAS  Google Scholar 

  • Greenman Y, Tordjman K, Osher E, Veshchev I, Shenkerman G, Reider G II, … Stern N. Postoperative treatment of clinically nonfunctioning pituitary adenomas with dopamine agonists decreases tumour remnant growth. Clin Endocrinol (Oxf). 2005;63(1):39–44.

    Google Scholar 

  • Greenman Y, Cooper O, Yaish I, Robenshtok E, Sagiv N, Jonas-Kimchi T, … Stern N. Treatment of clinically nonfunctioning pituitary adenomas with dopamine agonists. Eur J Endocrinol. 2016;175(1):63–72. https://doi.org/10.1530/EJE-16-0206.

  • Herman V, Fagin J, Gonski R, Kovacs K, Melmed S. Clonal origin of pituitary adenomas. J Clin Endocrinol Metab. 1990;71:1427–30.

    Article  CAS  PubMed  Google Scholar 

  • Hong J, Ding X, Lu Y. Clinical analysis of 103 elderly patients with pituitary adenomas: trans-sphenoidal surgery and follow-up. J Clin Neurosci. 2008;15(10):1091–5. https://doi.org/10.1016/j.jocn.2007.11.003.

    Article  PubMed  Google Scholar 

  • Hoybye C, Rahn T. Adjuvant Gamma Knife radiosurgery in non-functioning pituitary adenomas; low risk of long-term complications in selected patients. Pituitary. 2009;12(3):211–6. https://doi.org/10.1007/s11102-008-0163-x.

    Article  PubMed  Google Scholar 

  • Iacovazzo D, Caswell R, Bunce B, Jose S, Yuan B, Hernandez-Ramirez LC, … Korbonits M. Germline or somatic GPR101 duplication leads to X-linked acrogigantism: a clinico-pathological and genetic study. Acta Neuropathol Commun. 2016;4(1):56. https://doi.org/10.1186/s40478-016-0328-1.

  • Iwai Y, Yamanaka K, Yoshioka K, Yoshimura M, Honda Y, Matsusaka Y, … Yasui T. [The usefulness of adjuvant therapy using gamma knife radiosurgery for the recurrent or residual nonfunctioning pituitary adenomas]. No Shinkei Geka. 2005;33(8):777–83.

    Google Scholar 

  • Jaffrain-Rea ML, Derome P, Bataini JP, Thomopoulos P, Bertagna X, Luton JP. Influence of radiotherapy on long-term relapse in clinically non- secreting pituitary adenomas. A retrospective study (1970–1988). Eur J Med. 1993;2(7):398–403.

    CAS  PubMed  Google Scholar 

  • Jaffrain-Rea ML, Di Stefano D, Minniti G, Esposito V, Bultrini A, Ferretti E, … Cantore G. A critical reappraisal of MIB-1 labelling index significance in a large series of pituitary tumours: secreting versus non-secreting adenomas. Endocr Relat Cancer. 2002;9(2):103–13.

    Google Scholar 

  • Jameson JL, Klibanski A, Black PM, Zervas NT, Lindell CM, Hsu DW, … Habener JF. Glycoprotein hormone genes are expressed in clinically nonfunctioning pituitary adenomas. J Clin Invest. 1987;80:1472–8.

    Google Scholar 

  • Kanner AA, Corn BW, Greenman Y. Radiotherapy of nonfunctioning and gonadotroph adenomas. Pituitary. 2009;12(1):15–22.

    Article  PubMed  Google Scholar 

  • Karamouzis I, Berardelli R, Prencipe N, Berton A, Bona C, Stura G, … Grottoli S. Retrospective observational analysis of non-irradiated non-functioning pituitary adenomas. J Endocrinol Invest. 2015;38(11):1191–7. https://doi.org/10.1007/s40618-015-0361-0.

  • Karavitaki N, Thanabalasingham G, Shore HC, Trifanescu R, Ansorge O, Meston N, … Wass JA. Do the limits of serum prolactin in disconnection hyperprolactinaemia need re-definition? A study of 226 patients with histologically verified non-functioning pituitary macroadenoma. Clin Endocrinol (Oxf). 2006;65(4):524–9.

    Google Scholar 

  • Kirsch M, Morz M, Pinzer T, Schackert HK, Schackert G. Frequent loss of the CDKN2C (p18INK4c) gene product in pituitary adenomas. Genes Chromosomes Cancer. 2009;48(2): 143–54.

    Article  CAS  PubMed  Google Scholar 

  • Klibanski A. Clinical practice. Prolactinomas. N Engl J Med. 2010;362(13):1219–26. https://doi.org/10.1056/NEJMcp0912025.

    Article  CAS  PubMed  Google Scholar 

  • Kottler ML, Seret-Begue D, Lahlou N, Assayag M, Carre MC, Lagarde JP, … Warnet A. The GnRH receptor gene is preferentially expressed in functioning gonadotroph adenomas and displays a Mae III polymorphism site [In process citation]. Clin Endocrinol (Oxf). 1998;49(1):115–23.

    Google Scholar 

  • Kovacs K, Horvath E, Van Loon GR, Rewcastle NB, Ezrin C, Rosenbloom AA. Pituitary adenomas associated with elevated blood follicle-stimulating hormone levels: a histologic, immunocytologic, and electron microscopic study of two cases. Fertil Steril. 1978;29(6):622–8.

    Article  CAS  PubMed  Google Scholar 

  • Kovacs K, Lloyd R, Horvath E, Asa SL, Stefaneanu L, Killinger DW, Smyth HS. Silent somatotroph adenomas of the human pituitary. A morphologic study of three cases including immunocytochemistry, electron microscopy, in vitro examination, and in situ hybridization. Am J Pathol. 1989;134(2):345–53.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lasolle H, Raverot G. Therapeutic innovations in endocrine diseases – part 3: temozolomide and future therapeutics for aggressive pituitary tumors and carcinomas. Presse Med. 2016;45(6 Pt 2):e211–6. https://doi.org/10.1016/j.lpm.2016.05.008.

    Article  PubMed  Google Scholar 

  • Lecoq AL, Kamenicky P, Guiochon-Mantel A, Chanson P. Genetic mutations in sporadic pituitary adenomas–what to screen for? Nat Rev Endocrinol. 2015;11(1):43–54. https://doi.org/10.1038/nrendo.2014.181.

    Article  CAS  PubMed  Google Scholar 

  • Lecoq AL, Bouligand J, Hage M, Cazabat L, Salenave S, Linglart A, … Kamenicky P. Very low frequency of germline GPR101 genetic variation and no biallelic defects with AIP in a large cohort of patients with sporadic pituitary adenomas. Eur J Endocrinol. 2016;174(4):523–30. https://doi.org/10.1530/EJE-15-1044.

  • Lee M, Marinoni I, Irmler M, Psaras T, Honegger JB, Beschorner R, … Pellegata NS. Transcriptome analysis of MENX-associated rat pituitary adenomas identifies novel molecular mechanisms involved in the pathogenesis of human pituitary gonadotroph adenomas. Acta Neuropathol. 2013;126(1):137–50. https://doi.org/10.1007/s00401-013-1132-7.

  • Lee CC, Kano H, Yang HC, Xu Z, Yen CP, Chung WY, … Sheehan JP. Initial Gamma Knife radiosurgery for nonfunctioning pituitary adenomas. J Neurosurg. 2014;120(3):647–54. https://doi.org/10.3171/2013.11.JNS131757.

  • Liscak R, Vladyka V, Marek J, Simonova G, Vymazal J. Gamma knife radiosurgery for endocrine-inactive pituitary adenomas. Acta Neurochir (Wien). 2007;149(10):999–1006. https://doi.org/10.1007/s00701-007-1253-7; discussion 1006.

    Article  CAS  Google Scholar 

  • Liu C, Li Z, Wu D, Li C, Zhang Y. Smad3 and phospho-Smad3 are potential markers of invasive nonfunctioning pituitary adenomas. Onco Targets Ther. 2016;9:2265–71. https://doi.org/10.2147/OTT.S99699.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lloyd RV, Kovacs K, Young JWF, Farrel WE, Asa SL, Trouillas J, Kontogeorgos G, … Horvath E. Tumours of the pituitary. In DeLellis RA, Lloyd RV, Heitz PU, Eng C, editors. Pathology and genetics of tumours of endocrine organs, vol. 8. 3rd ed. Lyon: IARC Press; 2004. p. 1–50.

    Google Scholar 

  • Losa M, Mortini P, Barzaghi R, Ribotto P, Terreni MR, Marzoli SB, … Giovanelli M. Early results of surgery in patients with nonfunctioning pituitary adenoma and analysis of the risk of tumor recurrence. J Neurosurg. 2008;108(3):525–32.

    Google Scholar 

  • Losa M, Picozzi P, Motta M, Valle M, Franzin A, Mortini P. The role of radiation therapy in the management of non-functioning pituitary adenomas. J Endocrinol Investig. 2011;34(8):623–9. https://doi.org/10.3275/7618.

    CAS  Google Scholar 

  • Losa M, Bogazzi F, Cannavo S, Ceccato F, Curto L, De Marinis L, … Scaroni C. Temozolomide therapy in patients with aggressive pituitary adenomas or carcinomas. J Neurooncol. 2016a;126(3):519–25. https://doi.org/10.1007/s11060-015-1991-y.

  • Losa M, Spatola G, Albano L, Gandolfi A, Del Vecchio A, Bolognesi A, Mortini P. Frequency, pattern, and outcome of recurrences after gamma knife radiosurgery for pituitary adenomas. Endocrine. 2016b. https://doi.org/10.1007/s12020-016-1081-8.

  • Magro E, Graillon T, Lassave J, Castinetti F, Boissonneau S, Tabouret E, … Dufour H. Complications related to the endoscopic endonasal transsphenoidal approach for nonfunctioning pituitary macroadenomas in 300 consecutive patients. World Neurosurg. 2016;89:442–53. https://doi.org/10.1016/j.wneu.2016.02.059.

  • Melmed S. Pathogenesis of pituitary tumors. Nat Rev Endocrinol. 2011;7(5):257–66. https://doi.org/10.1038/nrendo.2011.40.

    Article  CAS  PubMed  Google Scholar 

  • Melmed S. Pituitary tumors. Endocrinol Metab Clin N Am. 2015;44(1):1–9. https://doi.org/10.1016/j.ecl.2014.11.004.

    Article  Google Scholar 

  • Messerer M, Dubourg J, Raverot G, Bervini D, Berhouma M, George I, … Jouanneau E. Non-functioning pituitary macro-incidentalomas benefit from early surgery before becoming symptomatic. Clin Neurol Neurosurg. 2013;115(12):2514–20. https://doi.org/10.1016/j.clineuro.2013.10.007.

  • Mete O, Asa SL. Clinicopathological correlations in pituitary adenomas. Brain Pathol. 2012;22(4): 443–53. https://doi.org/10.1111/j.1750-3639.2012.00599.x.

    Article  PubMed  Google Scholar 

  • Mete O, Gomez-Hernandez K, Kucharczyk W, Ridout R, Zadeh G, Gentili F, … Asa SL. Silent subtype 3 pituitary adenomas are not always silent and represent poorly differentiated monomorphous plurihormonal Pit-1 lineage adenomas. Mod Pathol. 2016;29(2):131–42. https://doi.org/10.1038/modpathol.2015.151.

  • Miermeister CP, Petersenn S, Buchfelder M, Fahlbusch R, Ludecke DK, Holsken A, … Buslei R. Histological criteria for atypical pituitary adenomas – data from the German pituitary adenoma registry suggests modifications. Acta Neuropathol Commun. 2015;3:50. https://doi.org/10.1186/s40478-015-0229-8.

  • Milker-Zabel S, Debus J, Thilmann C, Schlegel W, Wannenmacher M. Fractionated stereotactically guided radiotherapy and radiosurgery in the treatment of functional and nonfunctional adenomas of the pituitary gland. Int J Radiat Oncol Biol Phys. 2001;50(5):1279–86.

    Article  CAS  PubMed  Google Scholar 

  • Mingione V, Yen CP, Vance ML, Steiner M, Sheehan J, Laws ER, Steiner L. Gamma surgery in the treatment of nonsecretory pituitary macroadenoma. J Neurosurg. 2006;104(6):876–83. https://doi.org/10.3171/jns.2006.104.6.876.

    Article  PubMed  Google Scholar 

  • Minniti G, Esposito V, Piccirilli M, Fratticci A, Santoro A, Jaffrain-Rea ML. Diagnosis and management of pituitary tumours in the elderly: a review based on personal experience and evidence of literature. Eur J Endocrinol. 2005a;153(6):723–35.

    Article  CAS  PubMed  Google Scholar 

  • Minniti G, Traish D, Ashley S, Gonsalves A, Brada M. Risk of second brain tumor after conservative surgery and radiotherapy for pituitary adenoma: update after an additional 10 years. J Clin Endocrinol Metab. 2005b;90(2):800–4.

    Article  CAS  PubMed  Google Scholar 

  • Minniti G, Traish D, Ashley S, Gonsalves A, Brada M. Fractionated stereotactic conformal radiotherapy for secreting and nonsecreting pituitary adenomas. Clin Endocrinol (Oxf). 2006;64(5):542–8. https://doi.org/10.1111/j.1365-2265.2006.02506.x.

    Article  CAS  Google Scholar 

  • Minniti G, Scaringi C, Poggi M, Jaffrain Rea ML, Trillo G, Esposito V, … Enrici RM. Fractionated stereotactic radiotherapy for large and invasive non-functioning pituitary adenomas: long-term clinical outcomes and volumetric MRI assessment of tumor response. Eur J Endocrinol. 2015;172(4):433–41. https://doi.org/10.1530/EJE-14-0872.

  • Molitch ME. Nonfunctioning pituitary tumors and pituitary incidentalomas. Endocrinol Metab Clin N Am. 2008;37(1):151–71, xi.

    Article  Google Scholar 

  • Molitch ME. Pituitary tumours: pituitary incidentalomas. Best Pract Res Clin Endocrinol Metab. 2009;23(5):667–75. https://doi.org/10.1016/j.beem.2009.05.001.

    Article  CAS  PubMed  Google Scholar 

  • Molitch ME. Diagnosis and treatment of pituitary adenomas: a review. JAMA. 2017;317(5): 516–24. https://doi.org/10.1001/jama.2016.19699.

    Article  PubMed  Google Scholar 

  • Murad MH, Fernandez-Balsells MM, Barwise A, Gallegos-Orozco JF, Paul A, Lane MA, … Montori VM. Outcomes of surgical treatment for nonfunctioning pituitary adenomas: a systematic review and meta-analysis. Clin Endocrinol (Oxf). 2010;73(6):777–91. https://doi.org/10.1111/j.1365-2265.2010.03875.x.

  • Mussnich P, Raverot G, Jaffrain-Rea ML, Fraggetta F, Wierinckx A, Trouillas J, … D’Angelo D. Downregulation of miR-410 targeting the cyclin B1 gene plays a role in pituitary gonadotroph tumors. Cell Cycle. 2015;14(16):2590–7. https://doi.org/10.1080/15384101.2015.1064207.

  • Newey PJ, Nesbit MA, Rimmer AJ, Head RA, Gorvin CM, Attar M, … Thakker RV. Whole-exome sequencing studies of nonfunctioning pituitary adenomas. J Clin Endocrinol Metab. 2013;98(4):E796–800. https://doi.org/10.1210/jc.2012-4028.

  • Nishioka H, Inoshita N, Mete O, Asa SL, Hayashi K, Takeshita A, … Yamada S. The complementary role of transcription factors in the accurate diagnosis of clinically nonfunctioning pituitary adenomas. Endocr Pathol. 2015;26(4):349–55. https://doi.org/10.1007/s12022-015-9398-z.

  • Nomikos P, Ladar C, Fahlbusch R, Buchfelder M. Impact of primary surgery on pituitary function in patients with non-functioning pituitary adenomas – a study on 721 patients. Acta Neurochir (Wien). 2004;146(1):27–35.

    Article  CAS  Google Scholar 

  • Ntali G, Capatina C, Grossman A, Karavitaki N. Clinical review: functioning gonadotroph adenomas. J Clin Endocrinol Metab. 2014;99(12):4423–33. https://doi.org/10.1210/jc.2014-2362.

    Article  CAS  PubMed  Google Scholar 

  • Ntali G, Capatina C, Fazal-Sanderson V, Byrne JV, Cudlip S, Grossman AB, … Karavitaki N. Mortality in patients with non-functioning pituitary adenoma is increased: systematic analysis of 546 cases with long follow-up. Eur J Endocrinol. 2015;174(2):137–45. https://doi.org/10.1530/EJE-15-0967.

  • O’Sullivan EP, Woods C, Glynn N, Behan LA, Crowley R, O’Kelly P, … Agha A. The natural history of surgically treated but radiotherapy-naive nonfunctioning pituitary adenomas. Clin Endocrinol (Oxf). 2009;71(5):709–14.

    Google Scholar 

  • Olsson DS, Buchfelder M, Schlaffer S, Bengtsson BA, Jakobsson KE, Johannsson G, Nilsson AG. Comparing progression of non-functioning pituitary adenomas in hypopituitarism patients with and without long-term GH replacement therapy. Eur J Endocrinol. 2009;161(5):663–9. https://doi.org/10.1530/EJE-09-0572.

    Article  CAS  PubMed  Google Scholar 

  • Olsson DS, Nilsson AG, Bryngelsson IL, Trimpou P, Johannsson G, Andersson E. Excess mortality in women and young adults with nonfunctioning pituitary adenoma: a Swedish nationwide study. J Clin Endocrinol Metab. 2015;100(7):2651–8. https://doi.org/10.1210/jc.2015-1475.

    Article  CAS  PubMed  Google Scholar 

  • Paek SH, Downes MB, Bednarz G, Keane WM, Werner-Wasik M, Curran WJ Jr, Andrews DW. Integration of surgery with fractionated stereotactic radiotherapy for treatment of nonfunctioning pituitary macroadenomas. Int J Radiat Oncol Biol Phys. 2005;61(3):795–808. https://doi.org/10.1016/j.ijrobp.2004.07.688.

    Article  PubMed  Google Scholar 

  • Palmieri D, D’Angelo D, Valentino T, De Martino I, Ferraro A, Wierinckx A, … Fusco A. Downregulation of HMGA-targeting microRNAs has a critical role in human pituitary tumorigenesis. Oncogene. 2012;31(34):3857–65. https://doi.org/10.1038/onc.2011.557.

  • Park P, Chandler WF, Barkan AL, Orrego JJ, Cowan JA, Griffith KA, Tsien C. The role of radiation therapy after surgical resection of nonfunctional pituitary macroadenomas. Neurosurgery. 2004;55(1):100–6; discussion 106-107.

    Article  PubMed  Google Scholar 

  • Petrovich Z, Yu C, Giannotta SL, Zee CS, Apuzzo ML. Gamma knife radiosurgery for pituitary adenoma: early results. Neurosurgery. 2003;53(1):51–9; discussion 59-61.

    Article  PubMed  Google Scholar 

  • Peverelli E, Giardino E, Treppiedi D, Meregalli M, Belicchi M, Vaira V, … Mantovani G. Dopamine receptor type 2 (DRD2) and somatostatin receptor type 2 (SSTR2) agonists are effective in inhibiting proliferation of progenitor/stem-like cells isolated from nonfunctioning pituitary tumors. Int J Cancer. 2017;140(8):1870–80. https://doi.org/10.1002/ijc.30613.

  • Picozzi P, Losa M, Mortini P, Valle MA, Franzin A, Attuati L, … Giovanelli M. Radiosurgery and the prevention of regrowth of incompletely removed nonfunctioning pituitary adenomas. J Neurosurg. 2005;102(Suppl):71–74.

    Google Scholar 

  • Pigny P, Henric B, Lahlou N, Christin S, Mazzuca M, Dewailly D, Boersma A. A gonadotroph adenoma with a high proportion of basic FSH isohormones by chromatofocusing. J Clin Endocrinol Metab. 1996;81(6):2407–8.

    CAS  PubMed  Google Scholar 

  • Plummer C, Henderson RD, O’Sullivan JD, Read SJ. Ischemic stroke and transient ischemic attack after head and neck radiotherapy: a review. Stroke. 2011;42(9):2410–8. https://doi.org/10.1161/STROKEAHA.111.615203.

    Article  PubMed  Google Scholar 

  • Pollock BE, Cochran J, Natt N, Brown PD, Erickson D, Link MJ, … Schomberg PJ. Gamma knife radiosurgery for patients with nonfunctioning pituitary adenomas: results from a 15-year experience. Int J Radiat Oncol Biol Phys. 2008;70(5):1325–9. https://doi.org/10.1016/j.ijrobp.2007.08.018.

  • Raappana A, Koivukangas J, Ebeling T, Pirila T. Incidence of pituitary adenomas in Northern Finland in 1992–2007. J Clin Endocrinol Metab. 2010;95(9):4268–75. https://doi.org/10.1210/jc.2010-0537.

    Article  CAS  PubMed  Google Scholar 

  • Ramirez C, Cheng S, Vargas G, Asa SL, Ezzat S Gonzalez B, … Mercado M. Expression of Ki-67, PTTG1, FGFR4, and SSTR 2, 3, and 5 in nonfunctioning pituitary adenomas: a high throughput TMA, immunohistochemical study. J Clin Endocrinol Metab. 2012;97(5):1745–51. https://doi.org/10.1210/jc.2011-3163.

  • Raverot G, Sturm N, de Fraipont F, Muller M, Salenave S, Caron P, … Brue T. Temozolomide treatment in aggressive pituitary tumors and pituitary carcinomas: a French multicenter experience. J Clin Endocrinol Metab. 2010a;95(10):4592–9. https://doi.org/10.1210/jc.2010-0644.

  • Raverot G, Wierinckx A, Jouanneau E, Auger C, Borson-Chazot F, Lachuer J, … Trouillas J. Clinical, hormonal and molecular characterization of pituitary ACTH adenomas without (silent corticotroph adenomas) and with Cushing’s disease. Eur J Endocrinol. 2010b;163(1):35–43. https://doi.org/10.1530/EJE-10-0076.

  • Raverot G, Jouanneau E, Trouillas J. Management of endocrine disease: clinicopathological classification and molecular markers of pituitary tumours for personalized therapeutic strategies. Eur J Endocrinol. 2014;170(4):R121–32. https://doi.org/10.1530/EJE-13-1031.

    Article  CAS  PubMed  Google Scholar 

  • Raverot G, Assie G, Cotton F, Cogne M, Boulin A, Dherbomez M, … Massart C. Biological and radiological exploration and management of non-functioning pituitary adenoma. Ann Endocrinol (Paris). 2015;76(3):201–9. https://doi.org/10.1016/j.ando.2015.04.005.

  • Reddy R, Cudlip S, Byrne JV, Karavitaki N, Wass JA. Can we ever stop imaging in surgically treated and radiotherapy-naive patients with non-functioning pituitary adenoma? Eur J Endocrinol. 2011;165(5):739–44. https://doi.org/10.1530/EJE-11-0566.

    Article  CAS  PubMed  Google Scholar 

  • Righi A, Agati P, Sisto A, Frank G, Faustini-Fustini M, Agati R, … Foschini MP. A classification tree approach for pituitary adenomas. Hum Pathol. 2012;43(10):1627–37. https://doi.org/10.1016/j.humpath.2011.12.003.

  • Roelfsema F, Biermasz NR, Pereira AM. Clinical factors involved in the recurrence of pituitary adenomas after surgical remission: a structured review and meta-analysis. Pituitary. 2012;15(1): 71–83. https://doi.org/10.1007/s11102-011-0347-7.

    Article  PubMed  Google Scholar 

  • Rogers A, Karavitaki N, Wass JA. Diagnosis and management of prolactinomas and non-functioning pituitary adenomas. BMJ. 2014;349:g5390.

    Article  PubMed  CAS  Google Scholar 

  • Ruebel KH, Jin L, Zhang S, Scheithauer BW, Lloyd RV. Inactivation of the p16 gene in human pituitary nonfunctioning tumors by hypermethylation is more common in null cell adenomas. Endocr Pathol. 2001;12(3):281–9.

    Article  CAS  PubMed  Google Scholar 

  • Sanno N, Oyama K, Tahara S, Teramoto A, Kato Y. A survey of pituitary incidentaloma in Japan. Eur J Endocrinol. 2003;149(2):123–7.

    Article  CAS  PubMed  Google Scholar 

  • Schalin-Jantti C, Valanne L, Tenhunen M, Setala K, Paetau A, Sane T, Kouri M. Outcome of fractionated stereotactic radiotherapy in patients with pituitary adenomas resistant to conventional treatments: a 5.25-year follow-up study. Clin Endocrinol (Oxf). 2010;73(1):72–7. https://doi.org/10.1111/j.1365-2265.2009.03755.x.

    Google Scholar 

  • Schernthaner-Reiter MH, Trivellin G, Stratakis CA. MEN1, MEN4, and carney complex: pathology and molecular genetics. Neuroendocrinology. 2016;103(1):18–31. https://doi.org/10.1159/000371819.

    Article  CAS  PubMed  Google Scholar 

  • Sheehan JP, Kondziolka D, Flickinger J, Lunsford LD. Radiosurgery for residual or recurrent nonfunctioning pituitary adenoma. J Neurosurg. 2002;97(Suppl 5):408–14.

    PubMed  Google Scholar 

  • Sheehan JP, Starke RM, Mathieu D, Young B, Sneed PK, Chiang VL, … Lunsford LD. Gamma Knife radiosurgery for the management of nonfunctioning pituitary adenomas: a multicenter study. J Neurosurg. 2013;119(2):446–56. https://doi.org/10.3171/2013.3.JNS12766.

  • Sherlock M, Ayuk J, Tomlinson JW, Toogood AA, Aragon-Alonso A, Sheppard MC, … Stewart PM. Mortality in patients with pituitary disease. Endocr Rev. 2010;31(3):301–42. https://doi.org/10.1210/er.2009-0033.

  • Shorts-Cary L, Xu M, Ertel J, Kleinschmidt-Demasters BK, Lillehei K, Matsuoka I, … Wierman ME. Bone morphogenetic protein and retinoic acid-inducible neural specific protein-3 is expressed in gonadotrope cell pituitary adenomas and induces proliferation, migration, and invasion. Endocrinology. 2007;148(3):967–75. https://doi.org/10.1210/en.2006-0905.

  • Simpson DJ, Bicknell JE, McNicol AM, Clayton RN, Farrell WE. Hypermethylation of the p16/CDKN2A/MTSI gene and loss of protein expression is associated with nonfunctional pituitary adenomas but not somatotrophinomas. Genes Chromosomes Cancer. 1999;24(4): 328–36.

    Article  CAS  PubMed  Google Scholar 

  • Simpson DJ, Hibberts NA, McNicol AM, Clayton RN, Farrell WE. Loss of pRb expression in pituitary adenomas is associated with methylation of the RB1 CpG island. Cancer Res. 2000;60(5):1211–6.

    CAS  PubMed  Google Scholar 

  • Sivakumar W, Chamoun R, Nguyen V, Couldwell WT. Incidental pituitary adenomas. Neurosurg Focus. 2011;31(6):E18. https://doi.org/10.3171/2011.9.FOCUS11217.

    Article  PubMed  Google Scholar 

  • Snyder PJ, Sterling FH. Hypersecretion of LH and FSH by a pituitary adenoma. J Clin Endocrinol Metab. 1976;42:544–50.

    Article  CAS  PubMed  Google Scholar 

  • Soto-Ares G, Cortet-Rudelli C, Assaker R, Boulinguez A, Dubest C, Dewailly D, Pruvo JP. MRI protocol technique in the optimal therapeutic strategy of non-functioning pituitary adenomas. Eur J Endocrinol. 2002;146(2):179–86.

    Article  CAS  PubMed  Google Scholar 

  • Tabaee A, Anand VK, Barron Y, Hiltzik DH, Brown SM, Kacker A, … Schwartz TH. Endoscopic pituitary surgery: a systematic review and meta-analysis. J Neurosurg. 2009a;111(3):545–54. https://doi.org/10.3171/2007.12.17635.

  • Tabaee A, Anand VK, Barron Y, Hiltzik DH, Brown SM, Kacker A, … Schwartz TH. Predictors of short-term outcomes following endoscopic pituitary surgery. Clin Neurol Neurosurg. 2009b;111(2):119–22. https://doi.org/10.1016/j.clineuro.2008.09.010.

  • Trivellin G, Daly AF, Faucz FR, Yuan B, Rostomyan L, Larco DO, … Stratakis CA. Gigantism and acromegaly due to Xq26 microduplications and GPR101 mutation. N Engl J Med. 2014;371(25):2363–74. https://doi.org/10.1056/NEJMoa1408028.

  • Trouillas J, Girod C, Sassolas G, Claustrat B, Lheritier M, Dubois MP, Goutelle A. Human pituitary gonadotropic adenoma; histological, immunocytochemical, and ultrastructural and hormonal studies in eight cases. J Pathol. 1981;135(4):315–36.

    Article  CAS  PubMed  Google Scholar 

  • Trouillas J, Girod C, Sassolas G, Claustrat B. The human gonadotropic adenoma: pathologic diagnosis and hormonal correlations in 26 tumors. Semin Diagn Pathol. 1986;3(1):42–57.

    CAS  PubMed  Google Scholar 

  • Trouillas J, Sassolas G, Loras B, Velkeniers B, Raccurt M, Chotard L, … Girod C. Somatotropic adenomas without acromegaly. Pathol Res Pract. 1991;187(8):943–9.

    Google Scholar 

  • Trouillas J, Labat-Moleur F, Sturm N, Kujas M, Heymann MF, Figarella-Branger D, … Calender A. Pituitary tumors and hyperplasia in multiple endocrine neoplasia type 1 syndrome (MEN1): a case-control study in a series of 77 patients versus 2509 non-MEN1 patients. Am J Surg Pathol. 2008;32(4):534–43.

    Google Scholar 

  • Trouillas J, Roy P, Sturm N, Dantony E, Cortet-Rudelli C, Viennet G, … Tabarin A. A new prognostic clinicopathological classification of pituitary adenomas: a multicentric case-control study of 410 patients with 8 years post-operative follow-up. Acta Neuropathol. 2013;126(1): 123–35. https://doi.org/10.1007/s00401-013-1084-y.

  • Tsang RW, Brierley JD, Panzarella T, Gospodarowicz MK, Sutcliffe SB, Simpson WJ. Radiation therapy for pituitary adenoma: treatment outcome and prognostic factors. Int J Radiat Oncol Biol Phys. 1994;30(3):557–65.

    Article  CAS  PubMed  Google Scholar 

  • Turner HE, Adams CB, Wass JA. Pituitary tumours in the elderly: a 20 year experience. Eur J Endocrinol. 1999a;140(5):383–9.

    Article  CAS  PubMed  Google Scholar 

  • Turner HE, Stratton IM, Byrne JV, Adams CB, Wass JA. Audit of selected patients with nonfunctioning pituitary adenomas treated without irradiation – a follow-up study. Clin Endocrinol (Oxf). 1999b;51(3):281–4.

    Article  CAS  Google Scholar 

  • van den Bergh AC, van den Berg G, Schoorl MA, Sluiter WJ, van der Vliet AM, Hoving EW, … Dullaart RP. Immediate postoperative radiotherapy in residual nonfunctioning pituitary adenoma: beneficial effect on local control without additional negative impact on pituitary function and life expectancy. Int J Radiat Oncol Biol Phys. 2007;67(3):863–9.

    Google Scholar 

  • Vargas G, Gonzalez B, Ramirez C, Ferreira A, Espinosa E, Mendoza V, … Mercado M. Clinical characteristics and treatment outcome of 485 patients with nonfunctioning pituitary macroadenomas. Int J Endocrinol. 2015;2015:756069. https://doi.org/10.1155/2015/756069.

  • Vasilev V, Rostomyan L, Daly AF, Potorac I, Zacharieva S, Bonneville JF, Beckers A. Management of endocrine disease: pituitary ‘incidentaloma’: neuroradiological assessment and differential diagnosis. Eur J Endocrinol. 2016;175(4):R171–84. https://doi.org/10.1530/EJE-15-1272.

    Article  CAS  PubMed  Google Scholar 

  • Verges B, Boureille F, Goudet P, Murat A, Beckers A, Sassolas G, … Calender A. Pituitary disease in MEN type 1 (MEN1): data from the France-Belgium MEN1 multicenter study. J Clin Endocrinol Metab. 2002;87(2):457–65. https://doi.org/10.1210/jcem.87.2.8145.

  • Wilson PJ, De-Loyde KJ, Williams JR, Smee RI. A single centre’s experience of stereotactic radiosurgery and radiotherapy for non-functioning pituitary adenomas with the linear accelerator (Linac). J Clin Neurosci. 2012;19(3):370–4. https://doi.org/10.1016/j.jocn.2011.07.025.

    Article  CAS  PubMed  Google Scholar 

  • Woollons AC, Hunn MK, Rajapakse YR, Toomath R, Hamilton DA, Conaglen JV, Balakrishnan V. Non-functioning pituitary adenomas: indications for postoperative radiotherapy. Clin Endocrinol (Oxf). 2000;53(6):713–7.

    Article  CAS  Google Scholar 

  • Wowra B, Stummer W. Efficacy of gamma knife radiosurgery for nonfunctioning pituitary adenomas: a quantitative follow up with magnetic resonance imaging-based volumetric analysis. J Neurosurg. 2002;97(Suppl 5):429–32. https://doi.org/10.3171/jns.2002.97.supplement.

    PubMed  Google Scholar 

  • Xekouki P, Szarek E, Bullova P, Giubellino A, Quezado M, Mastroyannis SA, … Stratakis CA. Pituitary adenoma with paraganglioma/pheochromocytoma (3PAs) and succinate dehydrogenase defects in humans and mice. J Clin Endocrinol Metab. 2015;100(5):E710–9. https://doi.org/10.1210/jc.2014-4297.

  • Yamada S, Asa SL, Kovacs K, Muller P, Smyth HS. Analysis of hormone secretion by clinically nonfunctioning human pituitary adenomas using the reverse hemolytic plaque assay. J Clin Endocrinol Metab. 1989;68(1):73–80.

    Article  CAS  PubMed  Google Scholar 

  • Yoshino A, Katayama Y, Ogino A, Watanabe T, Yachi K, Ohta T, … Fukushima T. Promoter hypermethylation profile of cell cycle regulator genes in pituitary adenomas. J Neurooncol. 2007;83(2):153–62.

    Google Scholar 

  • Yu B, Ji N, Ma Y, Yang B, Kang P, Luo F. Clinical characteristics and risk factors for headache associated with non-functioning pituitary adenomas. Cephalalgia. 2016. https://doi.org/10.1177/0333102416648347.

  • Zada G, Woodmansee WW, Ramkissoon S, Amadio J, Nose V, Laws ER Jr. Atypical pituitary adenomas: incidence, clinical characteristics, and implications. J Neurosurg. 2011;114(2): 336–44. https://doi.org/10.3171/2010.8.JNS10290.

    Article  PubMed  Google Scholar 

  • Zhao J, Dahle D, Zhou Y, Zhang X, Klibanski A. Hypermethylation of the promoter region is associated with the loss of MEG3 gene expression in human pituitary tumors. J Clin Endocrinol Metab. 2005;90(4):2179–86.

    Article  CAS  PubMed  Google Scholar 

  • Zhou Y, Zhong Y, Wang Y, Zhang X, Batista DL, Gejman R, … Klibanski A. Activation of p53 by MEG3 non-coding RNA. J Biol Chem. 2007;282(34):24731–42. https://doi.org/10.1074/jbc.M702029200.

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Acknowledgments

French Endocrinology Society Nonfunctioning Pituitary Adenoma Working Group Members.

Philippe Chanson (Paris-Kremlin-Bicêtre), Gérald Raverot (Lyon), Christine Cortet-Rudelli (Lille), Françoise Galland (Rennes), Fréderic Castinetti (Marseille), Sylvie Salenave (Paris-Kremlin-Bicêtre), Laure Cazabat (Boulogne-Billancourt), Luc Foubert (Suresnes), Jean-François Bonneville (Besançon), Stephan Gaillard (Suresnes), Anne Boulin (Suresnes), Emmanuel Sonnet (Brest), Marie-Christine Vantyghem (Lille), Guillaume Assie (Paris), Vincent Rohmer (Angers), Brigitte Delemer (Rennes), Jean-Louis Sadoul (Nice), Isabelle Raingeard (Montpellier), Jacqueline Trouillas (Lyon), Chiara Villa (Paris), Jean-Marc Kuhn (Rouen), Henry Dufour (Marseille), Anne Barlier (Marseille), Lorraine Clavier (Créteil), Rachel Desailloud (Amiens), Emmanuel Jouanneau (Lyon), Dominique Maiter (Bruxelles, Belgique), Catherine Massart (Rennes), Françoise Borson-Chazot (Lyon), Michèle D’herbomez (Lille), Bruno Estour (Saint-Etienne), Gilles Brassier (Rennes) Muriel Cogne (Saint-Denis, La Réunion), François Cotton (Lyon), Maud Lebas (Rouen), Lucie Abouaf (Lyon), Alain Vighetto (Lyon), Bernard Coche Dequéant (Lille), Patrick Toussaint (Amiens), Gwenaëlle Vidal-Trécan (Paris), Alexandre Vasiljevic (Lyon), and Hervé Lefebvre (Rouen).

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Authors and Affiliations

  1. Service d’Endocrinologie et des Maladies de la Reproduction and Centre de Référence des Maladies Hypophysaires Rares, Hôpital de Bicêtre, Hôpitaux Universitaires Paris-Sud, Assistance Publique-Hôpitaux de Paris, Le Kremlin Bicêtre, France

    Philippe Chanson, Anne-Lise Lecoq & Sylvie Salenave

  2. Faculté de Médecine Paris-Sud, Univ Paris-Sud, UMR S1185, Le Kremlin-Bicêtre, France

    Philippe Chanson & Anne-Lise Lecoq

  3. INSERM U1185, Le Kremlin-Bicêtre, France

    Philippe Chanson & Anne-Lise Lecoq

  4. Fédération d’Endocrinologie, Groupement Hospitalier Est, Hospices Civils de Lyon, Lyon, France

    Gerald Raverot

  5. INSERM U1028; CNRS UMR5292; Centre de Recherche Lyon Neuroscience, Université de Lyon, Lyon, France

    Gerald Raverot

  6. Service d’Endocrinologie, Université Aix Marseille, Hôpital de la Conception, Marseille, France

    Frédéric Castinetti

  7. Service d’Endocrinologie-Métabolisme, Centre Hospitalier et Universitaire de Lille, Lille, France

    Christine Cortet-Rudelli

  8. Service d’Endocrinologie, Diabétologie, Nutrition, CHU Rennes, Hôpital Sud, Rennes, France

    Françoise Galland

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  1. Philippe Chanson
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  2. Anne-Lise Lecoq
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  3. Gerald Raverot
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  4. Frédéric Castinetti
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  5. Christine Cortet-Rudelli
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  6. Françoise Galland
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  7. Sylvie Salenave
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Correspondence to Philippe Chanson .

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  1. Faculty of Medicine, Biochemistry and Molecular Biology Department, University of Santiago de Compostela, Santiago de Compostela, Spain

    Felipe F. Casanueva

  2. Department of Medical Sciences, University of Torino, Torino, Italy

    Ezio Ghigo

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Chanson, P. et al. (2018). Physiopathology, Diagnosis, and Treatment of Nonfunctioning Pituitary Adenomas. In: Casanueva, F., Ghigo, E. (eds) Hypothalamic-Pituitary Diseases. Endocrinology. Springer, Cham. https://doi.org/10.1007/978-3-319-44444-4_4

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  • DOI: https://doi.org/10.1007/978-3-319-44444-4_4

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